Chlorotrimethylsilane → (6R,7R)-7-[[(2Z)-2-(2-amino-5-chloro-1,3-thiazol-4-yl)-2-hydroxyiminoacetyl]amino]-8-oxo-3-(1H-pyrazol-4-ylmethylsulfanyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Under nitrogen atmosphere, trimethylsilylacetamide (39.4 g) and trimethylchlorosilane (0.76 ml) were added successively to a suspension of 7β-amino-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylic acid (9.4 g) in dichloromethane (100 ml) at 0° C. The mixture was refluxed for 1.5 hours, then cooled again to -15° C. with dry ice-acetate. 2-(5-Chloro-2-formylaminothiazol-4-yl)-2-(Z)-(acetoxyimino)acetyl chloride (12.6 g) was added portionwise to the mixture over 10 minutes at the same temperature. The whole mixture was stirred for 12 hours at 0° C., then poured into 100 ml of ice-cooled methanol. After the solvent was concentrated in vacuo, 17 ml of concentrated hydrogen chloride was added at 0° C., and stirred for 7 hours. The mixture was poured into water (400 ml) and the pH was adjusted to between 3.4 and 3.6 with 28% ammonium hydroxide, and stirred for 12 hours at 0° C. The resulting precipitate was collected by filtration, and chromatographed on HP-20 to afford 7β-[2-(2-amino-5-chlorothiazol-4-yl)-2-(Z)-(hydroxyimino)-acetamido]-3-[(pyrazol-4-yl)methylthio]-3-cephem-4-carboxylic acid (6.30 g) as crystals. The physical data was identical with that the object compound of Example 3.

Provenance & Evidence